The program of gene expression in a cell is controlled by a selected array of transcription factors that are activated in response to extracellular cues. We have cloned and characterized several transcription factors that bind to regulatory regions of the oligodendrocyte myelin genes. One such factor named MYT1 (myelin transcription factor 1), a novel member of the zinc finger superfamily, may be instrumental in early stages of oligodendrocyte development and myelin production as well as during regeneration, in each case by coordinating the expression of myelin genes. MYT1 is also expressed in rapidly proliferating, high-grade gliomas, and therefore an examination of MYT1 immunoreactivity may provide additional information to aid in detecting and diagnosing CNS tumors. Another member of the MYT1 family (named MYT1L) is not expressed in oligodendrocytes, but instead marks neurons at the time they are undergoing their terminal mitosis. The developmental expression and localization of these two multifingered zinc proteins suggests that each may play a role in the development of neurons and oligodendrocytes in the mammalian central nervous system, a possibility that is being investigated via a transgenic mouse strategy. Also, additional proteins that bind to the promoters of myelin genes have been identified in a yeast one-hybrid system; interacting proteins have been identified with a yeast two-hybrid system. Another protein that binds to the myelin proteolipid protein promoter, named MYT2, was found to have several unusual features: 1) the protein itself can be secreted from cells, an unusual event for a DNA-binding protein, 2) MYT2 can also recognize RNA in addition to specifically binding DNA, and 3) the mRNA transcript encoding MYT2 represents one of the exceptional cellular messages that contains an internal ribosome entry site, suggesting that this expression of MYT2 is highly regulated at the translational level. One of the extracellular cues that promotes oligodendrocyte gene expression is insulin-like growth factor (IGF-1). The ability of IGF-I to facilitate remyelination and limit perivascular inflammation in an animal model of multiple sclerosis (EAE) have prompted parallel studies of IGF-I in a spinal cord injury model. Using a rat contusion model, we have administered IGF-I and are currently evaluating the impact that this growth factor has on regeneration after injury.